A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative

Abstract Introduction The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.


| INTRODUCTION
The Global Allergy and Asthma European Network, GA 2 LEN, originally started in 2004 as the European Union network of excellence in collaboration with EAACI (European Academy of Allergy and Clinical Immunology), is the largest multidisciplinary network of research centres and clinical care in allergy and asthma.The ADCARE group is a sub network within GA 2 LEN for expertise in atopic dermatitis (AD) that collaborates in research and educational activities as well as in exchange of experience in novel and emerging approaches to treat severely affected patients.
AD is a common chronic inflammatory skin disease representing a lifelong disposition with variable clinical manifestations and expression.The prevalence rates might vary between studies depending on the geographical, genetic, and methodological differences.Cross-sectional surveys report point prevalence, ranging across countries from 2.1% to 4.9% in adults and from 2.7% to 20.1% in children. 1,2In The Odense Adolescents Cohort Study, AD persisted into adulthood in 50% of those diagnosed in school age. 3 A nationwide Norwegian health registry suggests an increase in the incidence rate of paediatric AD, especially among children younger than 1 year.
During the study period, more than 1 in 6 children younger than 6 years had, at some point, been affected by AD. 4 This represents a significant burden of the disease, warranting effective, efficient, and broadly applicable management strategies that appreciate the complex and variable nature of AD. 5 AD is a systemic inflammatory condition, including filaggrin deficiency-induced skin-barrier disruption and microbiome alteration.Targeting the pathogenesis of AD, a multifaceted approach, including skin hydration, measures to strengthen skin barrier integrity, topical anti-inflammatory and antipruritic therapy, antibacterial measures, and the elimination of exacerbating factors, can help achieve disease control and prevention of comorbidities.However, many factors limit consistent adherence to treatment plans, such as concerns about side effects, difficulty following time-intensive and complex skin care routines, the economic burden of therapies, and challenges with lifestyle modifications.Patients with AD have sleep problems very commonly and are also at higher risk of mental health disorders, such as attention-deficit/hyperactivity disorder, anxiety, depression, disorder of behaviour, autism, and suicide.The visible and chronic nature of AD impacts the quality of life and can contribute to psychological stress, which in turn is a known trigger of itch and skin flares, creating a challenging vicious cycle.[19][20][21] Accordingly, approaches have been developed in appreciation of the complex interplay among biological, psychological, behavioural, and dietary factors and the wide range of knowledge, skills, and support that patients and families require to effectively manage and cope with this condition. 6In consideration of the complex pathophysiology and heterogenous clinical phenotype of AD, more individualised preventative and therapeutic strategies are desirable. 22comprehensive consensus-based S2k-guideline for the treatment of children and adults with AD was published as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients.23 This guideline was upgraded to the S3 level and published in 2022.24,25 While evidence-based guidelines form the basis of AD management, treatment strategies that are used in daily practice are far from guidelines and show significant variation in different jurisdictions or geographical regions.Integrated care pathways (ICP) not only consider different guidelines but can also fill the gaps by providing an expert discussion result based on clinical practice experience of reallife patient treatment journeys.ICPs offer structured multidisciplinary plans for patient management and have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance and describing co-ordination of care.26 Hence, ICPs can also consider the different contexts of lower-and middle-income countries as reflected in national guidance.27 AIRWAYS ICPs are an example of a multidisciplinary approach to reduce the burden of chronic respiratory diseases, their mortality and multimorbidity, and in the long term to promote active and healthy aging (AHA).28,29 The non-governmental organisation Allergic Rhinitis and Its Impact on Asthma (ARIA) has promoted the integration of its recommendations in ICPs using mobile technology to reinforce self-management and the implementation of guidelines.[30][31][32] Following this successful example, a similar strategy of F I G U R E 1 (A) More than skin diseases-comorbidities in AD. 9-13 1 At present, US and Asian data indicate cardiometabolic diseases as a comorbidity of AD, while data from European patients do not support this. Lyphoma is controversially discussed-it is possible that the 'association' to AD is based on a misdiagnosis of early stages of CTCL.14 2 For example, hyper IgE syndromes, WAS and WAS-like conditions; IPEX and IPEX-like conditions, CBM-opathies (CARD11 deficiency, CARD14 deficiency, MALT1 deficiency).3 New data indicate autoimmune comorbidities in adults with AD, for example, rheumatoid arthritis, inflammatory bowel disease, and alopecia areata.15,16 4 Lymphoma is controversially discussed-it is possible that the 'association' to AD is based on a misdiagnosis of early stages of CTCL. (B) TAD multidisciplinary team.Please note the country-specific differences, for example, in some countries, children are usually not seen by the GP during their first years of life but by primary care pediatricians.Hence, pediatricians as well as AD specialists are included as primary care providers.AD, atopic dermatitis; CTCL, cutaneous T cell lymphoma.
digitally enforced ICPs has been proposed for the setting of AD, to translate guidelines into clinical practice and to treat AD in the context of allergic comorbidities including asthma and food allergy as well as non-allergic comorbidities such as inflammatory bowel disease and psychological disorders through the coordination between multidisciplinary teams.This publication represents the result of the GA 2 LEN ADCARE initiative based on three conference meetings.

| OBJECTIVES
The general objective of the AD-ICP working group is to provide a pragmatic and practical support to optimally manage the disease and its comorbidities globally.AD-ICPs do not duplicate existing professional guidelines or national prevention programs but aim to strengthen them where appropriate and to help improve adherence to guideline recommendations by translating them into practice, integrating aspects from different guidelines and adjusting them to real-world conditions in a dynamic way.ICPs also contain information on how to combine therapies for AD and related diseases.
A holistic approach is strived to improve multidisciplinary communication, including primary care, to improve clinician-patient communication and patient satisfaction, to empower patients and their caregivers, and to engage them following the concept of shared decision making.Accordingly, AD-ICPs are designed to be carried out by a multidisciplinary team including the support of technologyassisted patient activation by mobile health tools to enhance selfmanagement and adherence to guidelines and to serve as a platform for patients to share their experiences.
The detailed objectives, challenges, and unmet needs in the management of AD have been published separately. 33

| Expert discussion
GA 2 LEN ADCARE has taken the lead, informing upfront EAACI, EADV and WAO about the initiative and asking for their involvement in the future, requesting them to send delegates.Other societies will be informed and asked for involvement at a later stage.
The core of the AD-ICP working group consists of speakers at an online conference held on 26 March 2020.Based on the results of the discussion of several specific working subgroups, the ICPs were then comprised following a structure with boxes indicating the different levels at which certain knowledge and interventions are required.
A second meeting was held on the 12 and 13 of August 2021 with dedicated workshops regarding different topics.Afterwards the document was circulated with all GAL 2 EN ADCARE centres.

| Stakeholders
The document involves all stake holders, including the patients, pharmacists, nurses, general practitioners and pediatricians, specialist, tertiary referral centres, the hospitals, academic research institutions, the pharmaceutical industry, and patient organisations.
Additional stakeholders not involved in the preparation of the document but included as discussion partners are healthcare institutions, healthcare providers and policy makers.
The document also supports the EU efforts on healthy and active aging (AHA) with GA 2 LEN being a partner in the EIP initiative on AHA.

| ATOPIC DERMATITIS INTEGRATED CARE PATHWAYS
Due to variable clinical manifestations, the variety of available treatments, and in order to become comfortable to take over responsibility for the treatment of their chronic condition, patients and their caregivers need clear and easy-to-understand strategies for their individual needs that will allow them to assess, ask, adjust and act. 6fferent levels of support are available to assist patients in the management of their disease.Figures 2A-H and 3 outline the ICPs for AD involving all stakeholders and self-management aspects for supporting patients with AD.Patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems.While the AD-ICPs aim to include as many stakeholders as possible, country-specific differences need to be considered, such as the role of nurse practitioners, which does not exist in all countries.Also, in some countries, children are usually not seen by the GP during their first years of life but by primary care pediatricians. 41Also, a large proportion of all patients with AD suffer from a mild form of the disease and could be managed mainly by the GP, primary care pediatrician and nurse practitioners.
Pharmacists are a further, valuable source of support, especially for patients with mild disease, and should therefore be more involved in AD care.
Adherence to AD therapy is often poor, particularly to adequate moisturiser application and to topical corticosteroid (TCS) treatment, the latter mainly due to the fear of side effects and steroid withdrawal symptoms. 42,43GPs and primary care pediatricians are in a key position to improve compliance before specialist referral and the next treatment steps to more potent therapies are considered.Patients need to be educated to build up the competence and the confidence to consequently manage acute flares and long-term maintenance treatment, which is known to effectively promote disease control. 44tients with AD have a high risk of atopic as well as non-atopic comorbidities (Figure 1A).For example, they have a significant and disease severity-dependent increased risk of the development of ocular morbidities, which might affect 25%-42% of AD patients.
6][47] Awareness and early referral to a dedicated specialist in case of any suspicion is paramount.
Of equal importance and often overlooked are psychosomatic and psychiatric morbidities such as sleep disturbances in time and quality, anxiety, and depression. 48Effective screening should systematically be part of AD management and therefore has been included in the AD-ICPs.

| Diagnostics in AD-Should treatment targets be based on clinical scores, or on symptoms/QoL? What is feasible in a daily practice setting?
In the primary care setting, diagnosing, and staging of AD should be based on clinical criteria including the assessment of itching and sleep disturbance using visual analogue scales and overall quality of life.An adaptation of the diagnostic approach to the patients' age is required.
The recommended diagnostic tool should be simple and could be supported by digital applications.Differential diagnosis is important and potentially challenging, as for example, early stages of cutaneous T-cell lymphoma might be misdiagnosed in patients with AD. 49 Criteria for AD specialist referral (see Figure 1B) should be provided considering the distribution pattern (localised vs. widespread, extent and localisation of affected body surface area), the need for daily treatment for several weeks, the need for high potency steroids, the response to treatment, the recurrence of symptoms, infections, the presence of comorbidities, the age of disease onset, and the impact on quality of life.
Scores, such as SCORAD, EASI, POEM, or DLQI/cDLQI, should be reserved for specialists as training in using these scoring systems is crucial.

| Comorbidities in AD
Atopic and non-atopic comorbidities have a considerable impact on disease burden and treatment options and require a multidisciplinary, integrated concept for their prevention, early detection, monitoring, and treatment (Figure 1A).[11] For example, contact allergies in patients with AD require consideration when choosing the type of topical treatment.With regard to food allergies, it is important to distinguish between small children and adults, between immediate and delayed reactions, and between allergy and intolerance for a better description of the potential phenotype of AD that may have implications for different systemic therapies.
The knowledge on non-atopic comorbidities in AD is increasing; however, the associations are not yet fully understood.For example, new data indicate autoimmune comorbidity in adults with AD, especially autoimmune dermatological, gastrointestinal and rheumatological diseases. 15,16Furthermore, the potential link of the metabolic syndrome to Th-1 inflammation should be addressed.[52] As an example of multidisciplinary efforts, an Italian team created a patient questionnaire in order to detect type 2 inflammatory disorders and to guide subsequent multidisciplinary management. 53 -9 of 23 A holistic approach and an investment in integrated mental health services are required to address the higher risk for psychological stress, sleep, and mental health disorders, such as attentiondeficit/hyperactivity disorder, anxiety, depression, disorder of behaviour, autism, and suicide.

| Rare but severe ocular comorbidities
Ophthalmological symptoms in patients with AD may be under detected and underestimated, all the more as patients can be asymptomatic.To diagnose and treat ocular comorbidities in AD, ophthalmological symptoms should be detected by careful history taking of the patient.These could be itchy eyes, pain, tearing, red eyes, rubbing, and disturbance of vision.
To prevent ocular comorbidity, it is important to treat periocular/eyelid eczema adequately to prevent corneal damage.Topical calcineurin inhibitors (TCI) are the first choice of treatment.Use of TCS on the eyelids can have deleterious effects on the incidence of ocular disease.In this case, high eye pressure should be screened because high corticosteroid intraocular pressure responsiveness is approximately 5% in the general population. 54 treat conjunctivitis, dermatologists/allergologists can prescribe artificial tears and antihistamine/mast cell stabiliser eye drops (preferably without preservatives).Corticosteroid eye drops should preferably be prescribed by an ophthalmologist.
Patients should be referred promptly to an ophthalmologist in the case of pain, photophobia, or vision loss, all of which could indicate keratitis/uveitis.Patients should be referred non-acutely (i) in case of moderate-to-severe AD and eyelid eczema/facial involvement, which is difficult to control, (ii) if eyelid eczema requires repeated use of TCS or maintenance TCS, or (iii) if conjunctivitis during biological treatment is not responding to artificial tears and TCI on the eyelids, or (iv) before starting a systemic therapy.As dedicated ophthalmologists are sparse, it is important to formulate precise referral criteria. [47]

| Topical treatment-Health care provision: Needs and limitations
Dysbiosis and the spectrum of sensitisation, especially mold (fungi), are important in the contemporary concept of barrier impairment in AD and influence the choice of topical treatment. 55,56pical treatment encompasses the preventative and supportive use of baseline therapeutics such as emollients and emollients 'plus', the latter containing saponins, flavonoids, riboflavins or bacterial lysates.Even for basic treatment with emollients, high costs can be a problem depending on economic status.In some places, there are also local cheaper alternatives that could be used potentially.In India, for example, coconut oil is often used but patients should be advised that low-quality substitutes may also have negative effects like contact allergy.
Topical treatment also includes anti-inflammatory substances such as corticosteroids and calcineurin inhibitors.For topical steroids, it is recommended to use primarily the more modern substances like mometasone, which have a lower level of cutaneous adverse events and do not lead to systemic levels. 57e rationales, advantages, and limitations of treatment with topical therapies in AD are summarised in Table 1.Topical treatments are indicated as recommended by the guidelines and should be optimised before changing the type of therapy.The transition points from topical treatments have been laid out in the European guideline and in IEC recommendation papers. 24,25,39,58However, it must be noted that treating large areas of the body with topical treatment has a severe negative impact on the quality of life and can influence the decision to move for systemic care.
Access to drugs is mostly good but varies by country, for example, in some countries a limited use of TCI was noted.In addition, reimbursement systems differ between countries and can further limit effective treatment.Even if reimbursement is given, guideline compliance shows large gaps, mostly due to the physicians' prescribing patterns.Concerns from both, patients and physicians, about the adverse effects of corticosteroid can limit effective treatment.Regular training of primary care clinicians by specialists could help to close these gaps.
In conclusion, there is a clear differential need for topical treatment in AD with mostly preventive, curative, or supportive reasons.There is a consensus about the criteria for using topical versus systemic treatment.Optimising treatment before switching is key.However, the current health care quality of AD with topical treatments is diverse and the benefits of topical treatments in individual patients are highly variable.

| Systemic treatments in AD
Most patients with mild-to-moderate AD respond adequately to optimised topical treatment and avoidance of exacerbating factors.
The management of bacterial, viral and/or fungal skin infections is of major importance as they can be the cause of acute exacerbations of disease severity or resistance to treatment.
However, many patients may not have adequate disease control with topical treatment alone or in combination with phototherapy using UVB or UVA, which can be of value in selected cases.In these patients and those with moderate-to-severe AD, systemic therapy is needed to control skin inflammation.The decision when to start a systemic therapy can be difficult, given the known risks of traditional immunosuppressants, which may cause concern about infections, particularly during the COVID-19 pandemic. 39e availability of systemic drugs is subject to country-specific differences as well as payment and out-of-pocket costs in the private versus general health care sections.
Off label drugs still play a role in the management of AD.However, licensed therapies should be considered first.Several new therapies approved for the treatment of AD are available, such as biologicals (dupilumab and tralokinumab) and JAK inhibitors (baricitinib, upadacitinib and abrocitinib).[61] The choice of systemic treatment in AD is dependent on the patients' age, efficacy, safety, comorbidities, and also the economic burden of the treatment (Table 2).Furthermore, specific concerns exist for some of the new agents and treating physicians should be familiar with the contraindications and appropriate laboratory follow up.
For certain patient subgroups, specific internationally published recommendations for systemic treatments exist, for example, for patients with comorbidities (e.g.asthma, rheumatoid arthritis), pregnancy, history of cancer, and planned vaccinations.Further subgroups require specific considerations, such as elderly patients and breastfeeding mothers.
Children and adolescents as a target group require special attention to safety aspects and for some substances specific adverse effects need to be considered, for example, for methotrexate.
However, particularly in adolescents, the impact of AD on the quality of life is considerably high and may differ from other age groups. 62Furthermore, adequate disease control in children and adolescents may affect the allergy march. 63Fortunately, novel treatments, such as dupilumab, are now also available for pediatric patients.

| New and emerging treatments: Biologics
The ideal aim is complete control by modern treatment achieving symptom-free life while acknowledging that this cannot be easily achieved in a complex, chronic immune-mediated inflammatory disease.In that case, there must be a joint discussion between the physician and patient about what is the realistic treatment aim, for example, aiming for symptom-free subthreshold eczema as well as the avoidance of flare ups.
Applications of newly developed drugs in clinical studies or already in daily practice show substantial progress in the treatment of moderately-to-severely affected patients with AD not responsive to standard topical treatments with corticosteroids or calcineurin inhibitors alone.Moreover, novel treatment approaches generate new knowledge about the (anti)inflammatory effects of immune modulation in AD and the heterogeneity of patient subgroups, which may stimulate further innovations in this field.
When evaluating new therapies for AD, special importance is attached to the assessment of patient-related outcomes.For the future, drugs highly effective for symptoms such as pruritus with a good benefit/risk ratio, with the possibility of individual dosing, and a rapid effect on symptom improvement after initiation of therapy are desired.
Dupilumab was the first specific therapeutic monoclonal antibody approved for the treatment of AD in 2017.The AD TREAT Germany registry demonstrated that dupilumab to date is by far the most prescribed systemic drug for AD with proven efficacy. 41,60,64,65Since autumn 2020, three JAK inhibitors have been approved for the treatment of AD in Europe (baricitinib, upadacitinib and most recently abrocitinib). 61,66Moreover, the anti-IL-13 specific monoclonal antibody tralokinumab was approved for the treatment of AD in adults. 67ile dupilumab is approved for adults as well as children, the benefits and safety of monoclonal antibodies and JAK inhibitors in moderate-tosevere AD in children and adolescents are still under investigation. 68though anti-IgE treatment is effective in some patients with asthma, it has not been proven to be effective in patients with AD so far. 69,70e efficacy of house dust mite (HDM) sublingual immunotherapy (SLIT) has been shown in patients with airway allergic diseases.Over the last years, several randomised controlled studies demonstrated that HDM SLIT represents an additional therapeutic tool for the treatment of mild-to-moderate AD in selected patients with comorbid-allergic rhinitis and/or asthma. 71,72 far, it is still unclear what patients benefit most from which systemic therapy.The guidance on the treatment approach in patients with moderate-to-severe AD and those with comorbidities is an important future task.Many of the newly licensed as well as emerging treatments have a positive effect not only on AD but also on atopic and non-atopic comorbidities.
Table 2 gives an overview of the currently licensed treatments for AD and/or other allergic comorbidities.
Short comparative trials are available; however, most treatments have not been compared head-to-head yet. 59In acknowledgment of the rapidly increasing evidence for a variety of emerging new therapies, an international group of clinicians, scientists and patients has conducted a living systematic review and network meta-analysis to provide relative efficacy, safety and impact on quality of life for available treatments.The results are updated regularly and made easily accessible on the website www.eczematherapies.comfor patients and clinicians. 73 present, no treat-to-target framework exists to guide the optimal use of systemic therapies in AD.As the current evidencebase for specific recommendations is still sparse, an international consensus framework was sought based on expert opinion and informed by extensive clinical experience.A clinical algorithm has been proposed to guide shared decision-making for systemic treatment, continuation, modification, or discontinuation in adults with moderate-to-severe AD.This work is intended to be a starting point and foundation to inform and stimulate a wider debate. 58

| AD in the pediatric population
Cohort studies demonstrate a cumulative incidence of 22.8% in children aged 0-6 years and an AD lifetime prevalence of 21.3% in adolescents and 34.1% in adults. 3,74,75ecial considerations in the pediatric population concern the complex interrelations between an evolving disease with different phenotypes and endotypes, a developing child, the maturation of skin, the immune system, and metabolism.
A correct diagnosis considering frequent and rare differential diagnoses needs to be ensured by a specialist when needed.Food allergies and immunodeficiencies must be considered in patients with severe and/or persistent courses, particularly in patients with an early onset.Children with severe and/or therapy-resistant AD in combination with high IgE levels and/or hypereosinophilia should be investigated for genetic inborn errors of immunity with the expertise of allergologists, immunologists, and geneticists. 76rthermore, parents' perceptions should be considered, treatment safety assessed by age, long-term disease control achieved, and comorbidities recognised early and prevented when possible.It is important to look at the complex interaction the disease has both on the family life as well as its impact on the life of the child itself when for instance at school.
Basic skin care and topical treatment should be chosen considering the safety, tolerability, hypoallergenic properties, and parent and child's acceptance.Pruritus control is an important therapy goal.
A personalised written action plan and team-school training to build ZUBERBIER ET AL.
-13 of 23 self-confidence and support self-management should be provided for patients and caregivers. 20,23in-barrier dysfunction can be apparent in the first weeks of life before the development of AD, suggesting that interventions to improve skin barrier function from infancy have the potential to prevent the skin condition. 77Gentle skin care for newborns supports skin function and ongoing postnatal skin maturation.Hence, recommendations on bathing and skin moisturisation, umbilical cord and diaper area care, and sun protection should be given to parents by midwives, nurses, and physicians. 78However, a Cochrane meta-analysis concluded that skin care interventions such as emollients during the first year of life in healthy infants are probably not effective in preventing AD.Further work is needed to understand whether different approaches to infant skin care might promote or prevent AD. [79][80][81]

| Living with the disease
AD is a chronic disease with different grades of severity, and it needs a reassessment of diagnostic features since new triggers may evolve, and an adaptation of the therapy may be needed.Ideally, depending on the grade or severity of AD, a physician should be in regular contact with the patient.The patient should also be empowered as much as possible to treat their own disease according to the fluctuating needs or disease status, but at the same time is trained enough at regular visits to assess these changes and triggers sensibly.This also includes early advising of parents about the prognosis of the disease and allergy prevention, for example, not smoking and early disease detection.

| The role of the pharmacist
Pharmacists should play a role in improving the patient's adherence with therapy, to reinforce and emphasise physicians' messages, and to prevent prescription mistakes (e.g.misdosing, incorrect drug name, individual patient contraindications) and drug-drug-interactions.
Currently, pharmacists mainly counsel on moisturisers and over the counter medications.The training of pharmacists is crucial considering the-phobia of patients and pharmacists.Specifically trained dermatological 'speciality' pharmacists within a pharmacy team would be desirable, providing the support outlined in Figure 2C.
The geographical variability of the resources and training will significantly affect the role the pharmacists play in AD treatment.In some countries, the role of an even highly specialised pharmacist in the context of systemic therapies is an important development.

| AN OUTLOOK FOR AD
While the AD-ICPs focus on the current situation, this concluding chapter aims at the future perspectives with potential implications for research activities.

| Limited resources
AD is increasing in prevalence in lower-and middle-income countries of Asia, Africa, Latin America, and the Middle East.Challenges include cost, access to care, and lack of specialists.Furthermore, most of the available diagnostic criteria and treatment guidelines are based on European and North American populations and only few trials report the ethnicity of the study population. 82Although AD presents similarly across racial and ethnic groups, some features may be different in patients with darker skin, as well as drug pharmacokinetics and adverse effects in different ethnicities are yet to be investigated.The unmet medical need for the management of AD in developing countries can be addressed by the training of specialists, improvement of access to and affordability of care. 83,84Furthermore, more financial support is needed for educational programs.This can save costs as well-educated patients can more easily control their disease.

| A personalised approach for AD patients
Despite its complex pathophysiology and variable clinical phenotype, AD is often considered a single disease and treated with a uniform approach.More tailored prevention and therapeutic strategies are being explored, such as by the BIOMAP Consortium, aiming to stratify AD patients according to their phenotype and endotype with the support of new biomarkers. 85,86Such a personalised approach may help to assign available and newly emerging drugs to those patients with the best benefit/risk ratio. 22Associations found using machine learning to perform deep phenotyping and identification of severity-associated factors might contribute to improving the monitoring of predisposed patients, and personalised disease management. 87

| Recent geopolitical developments, the impact of climate change on allergies and AD
[93] Patients suffering from AD triggered by pollen are more likely to be affected by these consequences of climate change.Furthermore, increasing heat waves are likely to be a trigger for more eczema exacerbations.Of note, both low and high ambient temperatures can increase the risk of outpatient visits. 94More exposure-response association analyses are needed to understand the effects of ambient temperature and eczema to develop preventive measures.Furthermore, no data are available on the effect of heat on local and systemic treatment of atopic eczema.

| ICPs by digital harmonisation
As part of a patient-centred approach, digitally supported ICPs could shorten the time to diagnosis, guide the patient in implementing the stepwise treatment plan and collect feedback from patients.They could also facilitate shared decision making between specialists.The existing MASK air app is the optimal app to add to comorbidities and AD.As a future perspective, this app should be embedded in other disease management systems.In the near-term future, digital health solutions could be provided at the government level in the national and other frequent languages for nomadic working citizens.

T A B L E 1
Rationale, needs and limitations for topical therapy in atopic dermatitis.Rationale � To prevent and improve barrier disruptions � To control inflammation � To restore and maintain the skin microbiome � To address specific problems such as itch, pain, superinfections, or exudation Advantages � Connection with the problem of barrier dysfunction � Efficiency when used adequately � Control of side effects � Flexible dosing and application modes � Versatility in including further compounds � General acceptance by most patients Limitations � Burden of time � No reimbursement from health insurances for basic therapy � High costs for some of the newer topical treatments Needs � Development of easy-to-use clinical scores to monitor treatment success as the validated scores such as SCORAD, EASI or DLQI are excellent in clinical trials but too time consuming for daily routine � Further criteria should be developed for decision making in step up or down in treatment: The objective and subjective burden, the patient's history, time course of the disease, the patient's preferences and response to topical treatment ZUBERBIER ET AL.